Researchers aimed to identify the characteristics, treatment pathways, and outcomes associated with epilepsy with eyelid myoclonia (EEM).
Epilepsy with eyelid myoclonia (EEM) is a rare and underrecognized generalized epilepsy.
In this review, researchers aimed to provide a comprehensive overview of EEM, including clinical presentations, evaluation, differential diagnosis, management, comorbidities, and outcomes.
The comprehensive narrative review was published in Epilepsy Research.
“With recent advances in epilepsy genetics and advances in novel drug treatment and neuromodulation for some epilepsy syndromes, it is important to update the clinical presentation, evaluation, and management of EEM to advance the recognition and timely diagnosis of the syndrome to improve management and outcome,” wrote the researchers of this study. “This comprehensive narrative review focuses on the epilepsy syndrome EEM, as opposed to the seizure type eyelid myoclonia, which is required for the diagnosis of EEM but may also be seen in other epilepsies.”
EEM was first recognized as a distinct epilepsy syndrome in 1977. EEM is characterized as eyelid myoclonia with or without absence seizure, eye closure induced seizures of electroencephalogram (EEG) paroxysms, and clinical or EEG photosensitivity.
According to one study, the prevalence of EEM among patients with epilepsy is around 1.2% and 2.7%. Another study found that 12 of 601 (5.6%) of individuals with generalized epilepsy had EEM. Variable forms of EEM have included early onset typical, early onset atypical, mild, classical, nonconvulsive status epilepticus, and EEM overlap with juvenile myoclonic epilepsy (JME). Furthermore, recent papers classified Sunflower syndrome as a subtype of EEM.
Additionally, EEM is a generalized epilepsy that occurs in childhood and typically continues into adulthood. Most studies on EEM have reported an average age of onset of around ages 6 to 8 years, although onset ages 1 to 16 years have been reported as well. Moreover, EEM predominantly occurs in women, with studies reporting between 56% and 92% of patients being female. Furthermore, a family history of epilepsy was reported in 33% to 83% of cases.
Evaluation and Differential Diagnosis
The literary research also revealed an association between background activity on EEG and EEM. Patients with EEM frequently have events captured on routine EEGs. However, structural brain imaging, such as MRIs or CTs typically show normal or nonspecific changes unrelated to epilepsy, with some studies suggesting an MRI is not required to make the diagnosis.
Furthermore, a recent study found specific genetic mutations were recognized in a minority of patients in the SYNGAP1, NEXMIF, RORB, and CHD2 genes.
The review also suggests that EEM diagnoses is oftentimes delayed or misdiagnosed as another epilepsy. In a study of 70 patients, 77.1% were misdiagnosed, most commonly with childhood absence epilepsy and JME.
Management and Outcomes
Throughout the review, the researchers found no published randomized controlled trials on EEM treatment, with most limited to retrospective and observational case series. These studies and case reports support the use of valproic acid, lamotrigine, ethosuximide, levetiracetam, zonisamide, clobazam, clonazepam, and lacosamide in reducing or stopping seizures. In an open-label multicenter pilot trial of levetiracetam, 20 of 35 (80%) responded to treatment, with 6 who became seizure free and 15 patients experiencing more than a 75% reduction in seizures.
Furthermore, in a retrospective study of 172 patients, 108 (62.8%) achieved at least 2-year remission from all seizure types. However, earlier age of epilepsy onset may increase the risk of intellectual disability, psychiatric comorbidities, and drug resistant epilepsy. In another study, family history of epilepsy was associated with seizure freedom and another analysis of 70 patients found 45 (64.3%) had drug-resistant seizures.
“EEM is a generalized epilepsy syndrome that consists of eyelid myoclonia, eye-closure induced EEG paroxysms, and photosensitivity,” wrote the researchers. “Although the syndrome is rare, patients are frequently misdiagnosed. The etiology is genetic but heterogeneous with several different pathogenic variants identified in a minority of patients.”
Furthermore, the researchers highlight the need for further research supporting the management of the disease, as well as a better understanding of its pathophysiology to support better management strategies where drug-resistant epilepsy is common.
Smith KM, Wirrell EC, Andrade DM, et al. A comprehensive narrative review of epilepsy with eyelid myoclonia. Epilepsy Research. 2023;193:107147. doi:10.1016/j.eplepsyres.2023.107147